Original Article

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Length of Latency with Preterm Premature Rupture of Membranes before 32 Weeks’ Gestation

1 Department of Obstetrics and Gynecology, Northwestern University

Feinberg School of Medicine, Chicago, Illinois 2 Department of Obstetrics and Gynecology, The George Washington University Biostatistics Center, Washington, District of Columbia 3 Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham Alabama 4 Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 5 Department of Obstetrics and Gynecology, Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio 6 Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah 7 Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 8 Department of Obstetrics and Gynecology, University of Texas Health Science Center at Houston, Houston, Texas 9 Department of Obstetrics and Gynecology, Columbia University, New York, New York 10 Department of Obstetrics and Gynecology, University of Miami, Miami, Florida 11 Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas

Address for correspondence Alan M. Peaceman, MD, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, 250 East Superior Street, Suite 5-2175, Chicago, IL 60611 (e-mail: [email protected]).

Am J Perinatol 2015;32:57–62.

Abstract

Keywords

► latency ► premature rupture of membranes ► preterm birth

received December 4, 2013 accepted after revision February 16, 2014 published online May 12, 2014

Objective The objective of the article is to describe latency for patients with preterm premature membrane rupture (PPROM) between 240/7 and 316/7 weeks’ gestation. Study Design Secondary analysis of data collected prospectively in a multicenter clinical trial of magnesium sulfate for cerebral palsy prevention. Women with PPROM and fewer than six contractions per hour at enrollment who were candidates for expectant management (n ¼ 1,377) were included in this analysis. Length of latency was calculated in days by subtracting the time of delivery from the time of membrane rupture. Results At each week of gestation, median latency between 24 and 28 weeks was similar at approximately 9 days, but it was significantly shorter with PPROM at 29, 30, and 31 weeks (p < 0.001). In addition, the percentage of patients remaining

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DOI http://dx.doi.org/ 10.1055/s-0034-1373846. ISSN 0735-1631.

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Alan M. Peaceman, MD1 Yinglei Lai, PhD2 Dwight J. Rouse, MD, MSPH3 Catherine Y. Spong, MD4 Brian M. Mercer, MD5 Michael W. Varner, MD6 John M. Thorp, MD7 Susan M. Ramin, MD8 Fergal D. Malone, MD9 Mary J. O’Sullivan, MD10 Gary D.V. Hankins, MD11; and for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

Length of Latency after Preterm PROM

Peaceman et al.

undelivered at 7 days and 14 days was similar for PPROM between 24 and 28 weeks, but it decreased significantly after that. For each gestational age, the proportion of patients remaining pregnant declined in a fashion similar to an exponential pattern. Conclusion Median latency after PPROM is similar from 24 to 28 weeks’ gestation, but it shortens with PPROM at and after 29 weeks.

Preterm premature rupture of membranes (PPROM) complicates 3% of pregnancies and is a significant contributor to perinatal morbidity and mortality. This increase in morbidity and mortality is primarily related to the gestational age at which PPROM and subsequent preterm delivery occurs. Management before 34 weeks’ gestation usually involves antibiotic administration and expectant management in an effort to prolong pregnancy. Length of latency until delivery appears to be inversely related to the gestational age at which PPROM occurs, but little data exist to describe this relationship against the background of prophylactic antibiotics.1,2 Our research network conducted a trial evaluating the use of magnesium sulfate to prevent cerebral palsy in patients at high risk of early preterm delivery.3 Because the majority of women entered into this large randomized trial had PPROM and were managed expectantly, it afforded the opportunity to estimate gestational age–specific measures of latency in patients experiencing PPROM between 24 and 31 weeks’ gestation and who routinely received antibiotics for pregnancy prolongation.

Materials and Methods We conducted a secondary analysis of a clinical trial of magnesium sulfate for the prevention of cerebral palsy performed at the 20 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network.3 Participants were women with singleton or twin gestations at 240/7 to 316/7 weeks’ gestation and were at high risk for spontaneous preterm delivery because of rupture of the membranes, advanced preterm labor, or an indicated preterm delivery. They were randomly allocated to treatment with magnesium sulfate as a 6 g bolus followed by a constant infusion of 2 g per hour, or matching placebo. The primary study was approved by the institutional review board at all participating centers, and all patients gave informed consent. Within this cohort, 1,377 patients who experienced PPROM from 24 to 31 weeks were contracting less than six times per hour at the time of randomization, and were the subject of this analysis. Criteria for assignment of gestational age were standardized,4 as were criteria for the diagnosis of ruptured membranes. Neither the antibiotic treatment nor criteria for delivery were standardized, but antibiotics were routinely administered, and expectant management was routinely pursued until at least 32 weeks’ gestation or until the patient entered spontaneous labor, developed intrauterine infection or bleeding, or the fetal status was deemed nonreassuring. Study medication was stopped after 12 hours American Journal of Perinatology

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if the patient was undelivered and regular uterine contractions were not present. Certified research personnel collected information on the mother’s demographic features, medical history, social history at enrollment, and maternal and neonatal outcome data at delivery. Information on residual amniotic fluid volume and cervical length were not collected. Latency was measured from time of reported rupture of membranes until time of delivery in hours. Median latency was calculated for patients with rupture at each week of gestational age between 24 and 31 weeks, rounded down to the nearest whole week (e.g., 280/7 to 286/7 weeks grouped as 28 weeks). For each week of gestational age at the time of PPROM, the percentage of women remaining undelivered at 7 and 14 days after PPROM were also calculated. Data were analyzed using SAS (SAS Institute, Cary, NC). Wilcoxon rank sum test was used to compare the median difference and Cochran–Armitage trend test was used to evaluate the trend of proportion changes. Multivariable regression analysis (proportional hazards regression or logistic regression) was performed to determine clinical factors contributing to duration of latency. We used the proportional hazard regression to analyze the latency as the outcome. Then, we used the logistic regression to analyze a binary indicator (whether the latency is greater than 7  24 hours) as the outcome. We also used the logistic regression to analyze another similar binary indicator (whether the latency is greater than 14  24 hours) as the outcome. Twin gestation, nulliparity, and treatment group were considered for adjustment in the regression analysis.

Results Baseline maternal characteristics of the expectantly managed patients with PPROM are presented in ►Table 1. Approximately, 97% of patients were treated with antibiotics, and < 7% of patients delivered within 12 hours of randomization. Reasons for delivery included spontaneous labor (68%), infection (9%), nonreassuring fetal status (10%), and bleeding (2%). Information regarding the interval from time of PPROM to delivery is reported in ►Table 2, and illustrated in ►Fig. 1. At each week of gestation, median latency between 24 and 28 weeks was similar at approximately 9 days, but it was significantly shorter with PPROM at 29, 30, and 31 weeks (p < 0.001, Wilcoxon rank sum test). In addition, the percentage of patients remaining undelivered at 7 and 14 days were similar for PPROM between 24 and 28 weeks’ gestation but decreased significantly after that (p < 0.001 for both, Cochran–Armitage trend test). For all gestational ages evaluated, the proportion of patients remaining pregnant declined in an exponential pattern (data not shown). Multivariable analysis demonstrated twin gestation (hazard ratio, 1.58; 95% CI,

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0.5 (0.3–0.8)

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Abbreviations: CI, confidence interval; OR, odds ratio; PPROM, preterm premature membrane rupture. a Risk of latency being less than for those with PPROM at 24 weeks.

22%

59

0.5 (0.3–0.8)

21% 30%

0.8 (0.5–1.3) 1.0 (0.6–1.5)

34% 35%

Peaceman et al.

1.0 (0.7–1.6) 1.3 (0.8–2.1)

41%

1 (ref) OR (95% CI)

1.1 (0.7–1.7)

34% Undelivered 14d

36%

0.4 (0.3–0.6) 0.4 (0.3–0.7) 0.6 (0.4–0.9) 0.9 (0.6–1.4) 0.9 (0.6–1.3) 1.0 (0.6–1.6) 1 (ref)

0.9 (0.6–1.3)

42%

1.9 (1.5–2.3) 1.7 (1.4–2.1)

5.0 (2.0, 11.0)

44% 53%

1.5 (1.2–1.8) 1.2 (0.9–1.4)

62% 60%

1.1 (0.9–1.4) 1.0 (0.8–1.3)

64%

OR (95% CI)

Table 2 Interval in days (d) from time of PPROM to delivery

PPROM is a common pregnancy complication, and is the precipitating cause of a significant portion of all preterm deliveries. Previous studies have noted that latency with PPROM can last for weeks, and that PPROM at earlier gestations appears to have longer latency to delivery.1,2 However, little data exist to describe latency at specific gestational ages. We have taken the opportunity to utilize a large and welldescribed cohort of patients with PPROM to describe latency of PPROM occurring between 24 and 31 weeks’ gestation. We found that time from membrane rupture to delivery remains relatively constant from 24 to 28 weeks’ gestation at 8 to 10 days, and then decreases to 5 days at 31 weeks. Furthermore, the finding of exponential decay at each gestational age allows for prediction of likelihood of latency persisting to any point in the future. As an example, PPROM at 29 weeks’ gestational age has a median latency of approximately 8 days, and roughly 25% of patients will remain undelivered at approximately 16 days, and 12.5% at approximately 24 days. When considering duration of latency in this cohort, we examined the effect of treatment with magnesium sulfate. No significant difference was seen between the treatment and control groups with regard to length of latency. Whether this absence of difference is due to insufficient dosing or lack of benefit of magnesium sulfate for this purpose cannot be determined.5 Another interesting finding was the considerably shorter median latency in twin gestations. The number

26, N ¼ 138

Comment

1.0 (0.8–1.3)

27, N ¼ 169

1.29–1.94) but neither nulliparity nor treatment with magnesium sulfate was associated with shorter latency. For twin gestations, median latency for those with PPROM between 24 and 28 weeks (n ¼ 71) was 7.0 days (interquartile range, 2.0, 13.0) and for twin gestations with PPROM 29 to 31 weeks (n ¼ 33) median latency was 2.0 days (interquartile range, 1.0, 6.0). Median latency for the magnesium sulfate group was 7.0 days, compared with 8.0 days for patients in the placebo arm (p ¼ 0.13).

61%

In kg/m2.

1 (ref)

398 (28.9)

64%

104 (7.6)

Smoking during pregnancy, n (%)

Hazard ratio (95% CI)

Twins, n (%)

Undelivered 7d

459 (33.3)

7.0 (4.0, 15.0)

Nulliparous, n (%)

9.5 (5.0, 17.0)

36 (2.6)

8.0 (4.0, 19.0)

209 (15.2)

Other

9.5 (4.0, 26.0)

Hispanic

9.0 (4.0, 21.0)

522 (37.9)

9.0 (4.0, 21.0)

White

29, N ¼ 185

610 (44.3)

28, N ¼ 172

a

Black

30, N ¼ 181

Maternal race or ethnic group, n (%)

Median latency (d) (Q1, Q3)

26.6 (6.81)

25, N ¼ 166

26.5 (6.30)

Maternal prepregnancy body mass indexa (SD)

24, N ¼ 171

Mean maternal age, y (SD)

a

28.3 (2.30)

Gestational age (wk)

Mean weeks gestation at randomization (SD)

31, N ¼ 195

Table 1 Maternal baseline characteristics

5.0 (2.0, 12.0)

Length of Latency after Preterm PROM

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Length of Latency after Preterm PROM

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Fig. 1 Latency with preterm premature membrane rupture (PPROM) median latency in days (with interquartile range) by gestational age at PPROM.

of patients with twin gestations is too small to generate weekspecific ranges for latency, but counseling of patients in this situation should be different than for those patients with singleton pregnancy and PPROM. Currently, the most common approach to management of PPROM at < 34 weeks’ gestation is expectant management with antibiotics to prolong latency. This practice is based on the understanding that gestational age at delivery is the most important factor impacting neonatal outcome. However, some concerns have been raised recently regarding this approach, primarily because of the increasing risks of developing intrauterine infection with delaying delivery in the face of ruptured membranes and the concerns for neurologic injury associated with the fetal inflammatory response.6 We observed that less than half of patients with PPROM after 29 weeks’ gestation remained undelivered for more than a week, exposing the majority to risks of infection with uncertain benefit of pregnancy prolongation after completion of antenatal corticosteroids. Two recent studies have addressed this issue with mixed results regarding increasing neonatal complications being associated with longer latency.7,8 Manuck et al found that in patients with PPROM, infection but not latency was associated with major perinatal morbidity, whereas Melamed et al found higher rates of composite neonatal morbidity with latency greater than 7 days. Future studies regarding pregnancy prolongation could be helpful in determining the most beneficial management approach. Ultimately, it may be found that the risk-benefit ratio for expectant management is not constant between 24 and 34 weeks’ gestation, and different clinical approaches may be more appropriate.

Acknowledgments The project described was supported by grants from the Eunice Kennedy Shriver NICHD [HD27869, HD34208, HD34116, HD40544, HD27915, HD34136, HD21414, HD27917, HD27860, HD40560, HD40545, HD40485, HD40500, HD27905, HD27861, HD34122, HD40512, American Journal of Perinatology

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HD53907, HD34210, HD21410, HD36801, HD19897], MO1-RR-000080, and by the National Institute of Neurological Disorders and Stroke (NINDS) and does not necessarily represent the official views of the NICHD, NINDS, or the National Institutes of Health. The authors thank the following subcommittee members who participated in protocol development and coordination between clinical research centers (Allison T. Northen, MSN, RN), protocol/data management and statistical analysis (Elizabeth Thom, PhD and Steven Weiner, MS), and protocol development and oversight (Deborah G. Hirtz, MD, Karin Nelson, MD, and Kenneth J. Leveno, MD). In addition to the authors, other members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network are as follows: G. Mallett, M. Ramos-Brinson., and P. Simon from Northwestern University, Chicago, IL. J. C. Hauth, A. Northen, T. Hill-Webb, S. Tate, K. Nelson, and F. Biasini from University of Alabama at Birmingham, Birmingham, AL. L. Fullmer (Intermountain Healthcare), K. Anderson, A. Guzman (Intermountain Healthcare), M. Jensen, and L. Williams from University of Utah, Salt Lake City, UT. K. Leveno, M.L. Sherman, J. Dax, L. Faye-Randall, C. Melton, and E. Flores from University of Texas Southwestern Medical Center, Dallas, TX. M. Collin, G. VanBuren, C. Milluzzi, M. Fundzak, and C. Santori from Case Western Reserve University-MetroHealth Medical Center, Cleveland, OH. J. Iams, F. Johnson, M. B. Landon, C. Latimer, V. Curry, and S. Meadows from The Ohio State University, Columbus, OH. R. Wapner, A. Sciscione, M. M. DiVito, M. Talucci, S. Desai, and D. Paul from Thomas Jefferson University, Philadelphia, PA. B. M. Sibai, R. Ramsey, W. Mabie, L. Kao, and M. Cassie University of Tennessee, Memphis, TN. Y. Sorokin, G. S. Norman, D. Driscoll, B. Steffy, and M. P. Dombrowski from Wayne State University, Detroit, MI. P. J. Meis, M. Swain, K. Klinepeter, M. O’Shea, and L. Steele from Wake Forest University Health Sciences, Winston-Salem, NC. K. J. Moise, Jr., S. Brody, J. Bernhardt, and K. Dorman from University of North Carolina at Chapel Hill, Chapel Hill. L. C. Gilstrap, III, M. C Day, E. Gildersleve, F. Ortiz, and M. Kerr from University of Texas Health Science Center at Houston, Houston, TX. V. Pemberton, L. Paley, C. Paley, S. Bousleiman, and V. Carmona from Columbia University, New York, NY. M. C. Carpenter, J. Tillinghast, D. Allard, B. Vohr, L. Noel, and K. McCarten from Brown University, Providence, RI. M. Miodovnik, N. Elder, W. Girdler, and T. Gratton from University of Cincinnati, Cincinnati, OH. H. Moawad, M. Lindheimer, and P. Jones from University of Chicago, Chicago, IL. F. Doyle, C. Alfonso, M. Scott, and R. Washington from University of Miami, Miami, FL.

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Length of Latency after Preterm PROM

Disclosure The authors report no conflict of interest. The comments and views of the authors do not necessarily represent the views of the National Institute of Child Health and Human Development (NICHD). This article was presented at the 31st Annual Meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, February 7, 2011, to February12, 2011.

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References 1 Pasquier J-C, Rabilloud M, Picaud J-C, et al; DOMINOS Group. A

2

3

4

5 6

7

8

prospective population-based study of 598 cases of PPROM between 24 and 34 weeks’ gestation: description, management, and mortality (DOMINOS cohort). Eur J Obstet Gynecol Reprod Biol 2005;121(2):164–170 Dale PO, Tanbo T, Bendvold E, Moe N. Duration of the latency period in preterm premature rupture of the membranes. Maternal and neonatal consequences of expectant management. Eur J Obstet Gynecol Reprod Biol 1989;30(3):257–262 Rouse DJ, Hirtz DG, Thom E, et al; Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008;359(9):895–905 Carey JC, Klebanoff MA, Hauth JC, et al; National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. N Engl J Med 2000;342(8):534–540 Grimes DA, Nanda K. Magnesium sulfate tocolysis: time to quit. Obstet Gynecol 2006;108(4):986–989 Yoon BH, Romero R, Park JS, et al. Fetal exposure to an intraamniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 2000;182(3):675–681 Manuck TA, Maclean CC, Silver RM, Varner MW. Preterm premature rupture of membranes: does the duration of latency influence perinatal outcomes? Am J Obstet Gynecol 2009;201(4):e1–e6 Melamed N, Ben-Haroush A, Pardo J, et al. Expectant management of preterm premature rupture of membranes: is it all about gestational age? Am J Obstet Gynecol 2011;204(1):e1–e8

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T. Wen, L. A. Goodrum, G. R. Saade, G. L. Olson, H. M. Harirah, and E. Martin from University of Texas Medical Branch, Galveston, TX. O. Langer, E. Xenakis, D. Conway, and M. Berkus from University of Texas at San Antonio, San Antonio, TX. S. Caritis, T. Kamon (deceased), M. Cotroneo, and C. Milford from University of Pittsburgh, Pittsburgh, PA. E. A. Thom, S. J. Weiner, B. Jones-Binns, M. Cooney, M. Fischer, S. McLaughlin, K. Brunette, and E. Fricks from The George Washington University Biostatistics Center. D. Hirtz, and K. B. Nelson from National Institute of Neurological Disorders and Stroke, Bethesda, MD. S. Tolivaisa, D. McNellis, C. Catz, and K. Howell from Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD. J. Roberts, MFMU Network Steering Committee Chair, from University of Pittsburgh, Pittsburgh, PA.

Peaceman et al.

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Length of latency with preterm premature rupture of membranes before 32 weeks' gestation.

The objective of the article is to describe latency for patients with preterm premature membrane rupture (PPROM) between 24(0/7) and 31(6/7) weeks' ge...
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